Tick-borne encephalitis overview

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ilan Dock, B.S.

Overview

Tick-borne diseases are most often transmitted during a blood meal, either by a nymph of adult tick. Blood meals will occur with a higher rate of incidence from the late spring into the early fall, with the highest rate of tick-borne encephalitis viral (TBEV) infections during the early and late summer. The primary disease vector for TBEV is the Ixodidae tick family, found throughout most of Eurasia. The virus itself is a member of the flavivirus genus, with three distinct subtypes. The virus is a (+)ssRNA genome enclosed in a capsid protein. It begins by locating a host cell receptor. The virus is internalized through the process of endocytosis. During this time the virus hi-jacks the host cells replication machinery, in order to replicate many times within the host cell. Upon completion the cell releases many immature virions for further progression of the disease. Progression of the disease results in an infection of the central nervous system, with clinical manifestation such as meningitis and encephalitis.

Historical Perspective

Incidence of tick-borne encephalitis is documented as far back as 18th century Scandinavian church records. During the early years of this discovery, the Russian Ministry of Health launched expeditions to explore incidence within the Far East. These expeditions led to the development of a successful vaccine in the 1940's. The European strain afflicted many Czechoslovakian patients until the late 1940's when a vaccine had finally been administered. Incidence since has drastically decreased with minor spikes here and there in recent history. However recent outbreaks in Hungary and the Czech Republic have been tied to the consumption of unpasteurized dairy products versus an infected tick bite.

Classification

There are three distinct subtypes associated with the tick-borne encephalitis virus. They include a Siberian, a Far Eastern, and a European subtype. Each subtype infection will display with different clinical manifestations. Identifying the subtype responsible for infection may assist in predicting the overall severity of the disease.

Causes

Tick-borne diseases are most often transmitted during a blood meal, either by a nymph of adult tick. Blood meals will occur with a higher rate of incidence from the late spring into the early fall, with the highest rate of tick-borne encephalitis viral (TBEV) infections during the early and late summer. The primary disease vector for TBEV is the Ixodidae tick family, found throughout most of Eurasia. The virus itself is a member of the flavivirus genus, with three distinct subtypes. The virus is a (+)ssRNA genome enclosed in a capsid protein. It begins by locating a host cell receptor. The virus is internalized through the process of endocytosis. During this time the virus hi-jacks the host cells replication machinery, in order to replicate many times within the host cell. Upon completion the cell releases many immature virions for further progression of the disease.

Differentiating tick-borne encephalitis from other diseases

Tick-borne encephalitis must be differentiated form other tick-borne diseases as well as infections induced by the different subtypes of tick-borne encephalitis virus (TBEV). TBEV also shares a common disease vector with many other tick-borne diseases, therefore a healthcare provider must recognize the potential for multiple co-infections. Found below are tables outlining the clinical manifestations of TBEV subtypes as well as commonly transmitted tick-borne diseases.

Epidemiology and Demographics

Tick-borne encephalitis is endemic to regions within Europe and Asia. These areas include territories spanning from France to Northern Japan; and from Russia to Albania. Incidence is approximately 5,000 to 13,000 infections per year. Vaccination is a method of preventing the virus, however the virus will still persist at 1 case per 10,000 unvaccinated individuals. The majority of infections occur between April and November with the highest rates of infection in the early and late summer periods. There is a higher incidence of infection among individuals above the age of 50.

Risk factors

The primary risk factors associated with tick-borne encephalitis are exposure to endemic environments and the consumption of unpasteurized dairy products. More severe infections have been reported in individuals over the age of 50 years.

Natural history, complications, and prognosis

Tick-borne encephalitis commonly presents itself as a biphasic infection. Following an incubation period of 7 to 14 days, a patient will experience an early phase including non-specific flu like symptoms. Once early phase symptoms reside, a remission phase occurs in which a patient experiences lessened severity of symptoms or appears entirely asymptomatic. Infection will conclude at this point within nearly two-thirds of patients. However, a second phase will onset within the remaining one-third. This phase includes the infection of the central nervous system. Progression of the disease at this point will present itself as aseptic meningitis, encephalitis, or myelitis. Complications are commonly associated with this later phase, including the aforementioned meningitis and encephalitis as well as long term cognitive dysfunction and limb paresis. The prognosis is usually good for the majority of infected patients. Many patients will appear to be asymptomatic during the course of infection. For individuals displaying signs and symptoms, the clinical manifestations will typically reside after the first wave of non-specific flu like symptoms. However as mentioned earlier, a second phase can occur. The prognosis for patients undergoing this course of infection is still fairly good. Yet, patients experience an infection of the central nervous system are more prone to long term complications.

History and symptoms

Tick-borne encephalitis infections will often present themselves with biphasic clinical manifestations. Following an incubation period of 7 to 14 days, a patient will experience early onset, non-specific flu like symptoms. A patient will then experience a remission period of lessened symptoms or will appear to be completely asymptomatic. A second phase will occur in which patients will experience an infection of the central nervous system resulting in a number of neurological, clinical manifestations.

Physical examination

Early onset signs include fever, lethargy, and overall weakness. As the infection progresses, further clinical manifestations will present themselves in the form of tachycardia, changes in blood pressure, sensitivity of the eye and skin, and the appearance of a rash. Signs may appear to be similar to other diseases within the umbrella of tick-borne fevers however a biphasic infection period (early onset symptoms, remission period, and second phase of symptoms) is a characteristic sign of tick-borne encephalitis.

Laboratory findings

An array of laboratory tests exist to assist with the diagnoses of tick-borne encephalitis. Polymerase chain reactions are most effective during the first week of infection. An early detection as a result of a successful PCR enables quicker medical treatment and ultimately a potentially higher survival rate. Other test useful during the later stages of infection include immunofluorescence assays, antibody titers, ELISA, and other serologic tests.

Medical therapy

Treatments for tick-borne encephalitis may be categorized according to a mainstay, phosphrenyl treatment, an antibiotic therapy, and homeopathic, herbal treatments. Phosphrenyl treatment is similar to interferon treatment for Hepatitis C, utilized as both a therapeutic and prophylactic agent. Antibiotic therapies are useful as many disease vectors responsible for transmission of tick-borne encephalitis also carry many other tick-borne diseases. An antibiotic therapy may be helpful in anticipating any potential tick-borne co-infections. Antibiotics have also been useful in deactivating certain characteristics of the virus. However certain antibiotic therapies have proven to activate the virus. Thus for this reason, certain antibiotics, such as streptomycin, should not be prescribed during the course of infection. Homeopathic therapies, such as ledum, motherwort, and blackcurrant have inactivating effects on tick-borne encephalitis virus.

Prevention

Tick- borne encephalitis prevention strategies are based on avoiding potential, infected tick bites. Avoiding tick bites may be accomplished through limiting exposure to endemic areas. However if it is impossible or impractical to avoid these areas, several preventative strategies may be implemented. These strategies are indicated under the Prevention title below. Other prevention strategies include a proper removal of the tick. This process is also outlined below under the title, the best way to remove a tick.